Abstract

Supralethally irradiated dogs were reconstituted wth their own stored bone marrow and were challenged at various time intervals with a kidney allograft. The data suggest that transplanted bone marrow cells may participate directly in the events leading to allogenic unresponsiveness. The time interval between marrow cell replacement and kidney allotransplantation required for optimal results suggest that at least one cycle of cell turnover by the replaced stem cells is needed in order to produce unresponsiveness. Host irradiation and reconstitution with stored autologous marrow may be useful in the treatment of certain forms of cancer.

These results point to the capacity of suprelethal total-body irradiation and autologous bone marrow replacement to produce in the host a time-dependent privileged phase of immunologic reactivity during which exposure to alloantigens is more likely to produce unresponsiveness, rather than sensitization. The mechanisms implicated in the mediation of this phenomenon are not clear. Regardless of hypothetical interpretations, however, the current growing interest in total-body irradiation and autologous bone marrow replacement in clinical medicine, and the ease with which this approach appears to produce allogenic unresponsiveness in large mammals, raise the possibility that this method may constitute a highly promising approachmore » to the facilitation of survival of vital transplanted organs in man. This possibility is further supported by the long-term record of the world's longest surviving renal allograft recipient, whose preoperative preparation consisted of total-body irradiation 24 hr before a kidney transplant.« less

Data are presented to give the background of information used for the assessment of the potential applicability of supralethal total-body irradiation and bone-marrow replacement as a technique for the induction of allogeneic unresponsiveness in dogs. Three experimental models for this purpose are described. A table is presented to show the effects of the three methods of host pretreatment for the induction of allogeneic unresponsiveness. The standard and third-party methods induced unresponsiveness to tissues obtained from the donor of marrow. The data were consistent with the possibility that total-body irradiation may induce in the host a privileged phase of altered immunologicmore » reactivity during which antigenic challenge is more likely to produce unresponsiveness than sensitization. (HLW)« less

Hemopoietic reconstitution of supralethally irradiated adult dogs of the Cooperstown colony with their own stored bone marrow can produce long-term unresponsiveness to DLA-identical kidney allografts with no need for any additional immunosuppression. Eleven of 18 kidneys transplanted 12 h after replacement of autologous marrow into irradiated recipients currently survive with normal function for as long as 1417 d; 8 of 13 organs transplanted 28 h after marrow replacement, and 8 of 13 organs transplanted 36 h after marrow injection, currently survive up to 502 d, with no further treatment. Alterations in the timing and sequence of each procedure decrease themore » incidence of unresponsiveness. Survival and function of the kidney allografts were not affected by the rejection of successive skin grafts from the kidney donor. Skin grafts from other DLA-identical donors and DLA-incompatible skin grafts were rejected by the same recipients in uniform fashion.« less